Clinical, biochemical, and morphological correlates in patients bearing growth hormone-secreting pituitary tumors with or without constitutively active adenylyl cyclase

J Clin Endocrinol Metab. 1990 Dec;71(6):1421-6. doi: 10.1210/jcem-71-6-1421.


Somatic mutations in the alpha-chain (alpha s) of the stimulatory regulatory protein of adenylyl cyclase (Gs) causing constitutive activation of the enzyme have been identified in a subset of human GH-secreting pituitary adenomas. This study reports on the differences between acromegalic patients bearing tumors without (group 1; n = 51) or with (group 2; n = 29) this alteration. No difference in age, sex, clinical features, duration of the disease, or cure rate was observed between the two groups. By contrast, group 2 patients had higher basal GH levels than group 1. Moreover, a significant difference in sellar morphology was found; group 2 patients more frequently showed sellas of normal size (grade I) than group 1. Hypersecretory activity of group 2 tumors was also apparent at electron microscopy; contrary to those of group 1, cells of group 2 tumors were densely granulated and showed prominent rough endoplasmic reticulum and Golgi complex. With respect to group 1, group 2 patients were less responsive to GH-releasing hormone, while they were more sensitive to somatostatin- and dopamine-induced GH inhibition. These results suggest that patients with constitutively active adenylyl cyclase have hyperactive tumors; the sensitivity of these tumors to inhibitory agents (somatostatin and dopamine), possibly counteracting the expression of activating mutations, might explain the low rate of tumor growth.

MeSH terms

  • Acromegaly / enzymology
  • Adenoma / enzymology*
  • Adenoma / genetics
  • Adenoma / pathology
  • Adenylyl Cyclases / metabolism*
  • Adolescent
  • Adult
  • Aged
  • Cytoplasmic Granules / pathology
  • Dopamine / pharmacology
  • Endoplasmic Reticulum / pathology
  • Enzyme Activation / drug effects
  • Female
  • GTP-Binding Proteins / genetics*
  • Golgi Apparatus / pathology
  • Gonadotropin-Releasing Hormone / pharmacology
  • Growth Hormone / metabolism*
  • Humans
  • Male
  • Microscopy, Electron
  • Middle Aged
  • Mutation
  • Pituitary Neoplasms / enzymology*
  • Pituitary Neoplasms / genetics
  • Pituitary Neoplasms / pathology
  • Prognosis
  • Sella Turcica / pathology
  • Sodium Fluoride / pharmacology
  • Somatostatin / pharmacology
  • Thyrotropin-Releasing Hormone / pharmacology


  • Gonadotropin-Releasing Hormone
  • Somatostatin
  • Thyrotropin-Releasing Hormone
  • Sodium Fluoride
  • Growth Hormone
  • GTP-Binding Proteins
  • Adenylyl Cyclases
  • Dopamine